Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3

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Chacko, A
Sly, PD
Ware, RS
Begum, N
Deegan, S
Thomas, N
Gauld, LM
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Introduction: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown. Aim: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment. Methods: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test. Results: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen. Conclusion: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

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© The Author(s) 2021. This is the author-manuscript version of this paper. It is posted here with permission of the copyright owner(s) for your personal use only. No further distribution permitted. For information about this journal please refer to the publisher’s website or contact the author(s).
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Clinical sciences
paediatric lung disaese
paediatric physician
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respiratory measurement
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Chacko, A; Sly, PD; Ware, RS; Begum, N; Deegan, S; Thomas, N; Gauld, LM, Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3, Thorax, 2021